Expression of SARS-CoV-2 Entry Factors in the Pancreas of Normal Organ Donors and Individuals with COVID-19.
ACE2
CD34
COVID-19
SARS-CoV-2
TMPRSS2
insulin
islet
pancreas
type 1 diabetes
type 2 diabetes
Journal
Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170
Informations de publication
Date de publication:
01 12 2020
01 12 2020
Historique:
received:
01
09
2020
revised:
19
10
2020
accepted:
10
11
2020
pubmed:
19
11
2020
medline:
18
12
2020
entrez:
18
11
2020
Statut:
ppublish
Résumé
Diabetes is associated with increased mortality from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Given literature suggesting a potential association between SARS-CoV-2 infection and diabetes induction, we examined pancreatic expression of angiotensin-converting enzyme 2 (ACE2), the key entry factor for SARS-CoV-2 infection. Specifically, we analyzed five public scRNA-seq pancreas datasets and performed fluorescence in situ hybridization, western blotting, and immunolocalization for ACE2 with extensive reagent validation on normal human pancreatic tissues across the lifespan, as well as those from coronavirus disease 2019 (COVID-19) cases. These in silico and ex vivo analyses demonstrated prominent expression of ACE2 in pancreatic ductal epithelium and microvasculature, but we found rare endocrine cell expression at the mRNA level. Pancreata from individuals with COVID-19 demonstrated multiple thrombotic lesions with SARS-CoV-2 nucleocapsid protein expression that was primarily limited to ducts. These results suggest SARS-CoV-2 infection of pancreatic endocrine cells, via ACE2, is an unlikely central pathogenic feature of COVID-19-related diabetes.
Identifiants
pubmed: 33207244
pii: S1550-4131(20)30600-8
doi: 10.1016/j.cmet.2020.11.005
pmc: PMC7664515
pii:
doi:
Substances chimiques
ACE2 protein, human
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Serine Endopeptidases
EC 3.4.21.-
TMPRSS2 protein, human
EC 3.4.21.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1041-1051.e6Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK127308
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK127786
Pays : United States
Organisme : BLRD VA
ID : I01 BX001733
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI134971
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK097512
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI050237
Pays : United States
Organisme : NIDDK NIH HHS
ID : UC4 DK108132
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK093954
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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